Abstract
Two novel norcantharidin acylamide acids (HL1=N-pyrimidine norcantharidin acylamide acid, C12H13N3O4; HL2=N-pyridine norcantharidin acylamide acid, C13H14N2O4) were synthesized by a reaction of norcantharidin(NCTD) with 2-aminopyrimidine and 2-aminopyridine, respectively. Their structures were characterized by elemental analysis, IR, UV and 1 H NMR. Fluorescence titration and viscosity measurements indicated that HL1, HL2 and HL3 (HL3=N-phenyl norcantharidin acylamide acid, C14H15NO4) can bind calf thymus DNA via partial intercalation. The liner Stern-Volmer quenching constant Ksv values for HL1, HL2 and HL3 were 2.05 × 104 L mol−1, 1.15 × 104 L mol−1 and 8.30×103 L mol−1, respectively. Two compounds containing heterocycle of HL1 and HL2 have been found to cleave pBR322 plasmid DNA at physiological pH and temperature. The test of antiproliferation activity showed that the compounds had moderate to strong antiproliferative ability against the tested cell lines except of HL3 against the SMMC7721 cell line. The results indicated that the heterocycle attached to the norcantharidin was favorable to antiproliferative activity. This result was consistent with the DNA binding experiment.
[1] I. Kostova, G. Momekov, T. Tzanova, M. Karaivanova, Bioinorg.Chem. Appl. 2006, 25651 (2006) 10.1155/BCA/2006/25651Search in Google Scholar
[2] B.D. Wang, Z.Y. Yang, Q. Wang, T.K. Cai, P. Crewdsonc, Bioorg. Med. Chem. 14, 1880 (2006) http://dx.doi.org/10.1016/j.bmc.2005.10.03110.1016/j.bmc.2005.10.031Search in Google Scholar
[3] T.M. Ehrman, D.J. Barlow, P.J. Hylands, J. Chem. Inf. Model. 47, 2316 (2007) http://dx.doi.org/10.1021/ci700155t10.1021/ci700155tSearch in Google Scholar
[4] L. Janovec, D. Sabolova, M. Kozurkova, H. Paulikova, P. Kristian, J. Ungvarsky, E. Moravcikova, M. Bajdichova, D. Podhradsky, J. Imrich, Bioconjugate Chem. 18, 93 (2007) http://dx.doi.org/10.1021/bc060168v10.1021/bc060168vSearch in Google Scholar
[5] S.K.H. Huan, H.H. Lee, D.Z. Liu, C.C. Wu, C.C. Wang, Toxicology 223, 136 (2006) http://dx.doi.org/10.1016/j.tox.2006.03.01210.1016/j.tox.2006.03.012Search in Google Scholar
[6] T. Efferth, R. Rauh, S. Kahl, M. Tomicic, H. Bochzelt, M.E. Tome, M.M. Briehl, R. Bauer, B. Kaina, Biochem. Pharmacol. 69, 811 (2005) http://dx.doi.org/10.1016/j.bcp.2004.12.00310.1016/j.bcp.2004.12.003Search in Google Scholar
[7] A. McCluskey, M.C. Bowyer, E. Collins, A.T.R. Sim, J.A. Sakoff, M.L. Baldwin, Bioorg. Med. Chem. Lett. 10, 1687 (2000) http://dx.doi.org/10.1016/S0960-894X(00)00323-110.1016/S0960-894X(00)00323-1Search in Google Scholar
[8] G.S. Wang, J. Ethnopharmacol. 26, 147 (1989) http://dx.doi.org/10.1016/0378-8741(89)90062-710.1016/0378-8741(89)90062-7Search in Google Scholar
[9] A. McCluskey, A.T.R. Sim, J.A. Sakoff, J. Med. Chem. 45, 1151 (2002) http://dx.doi.org/10.1021/jm010066k10.1021/jm010066kSearch in Google Scholar PubMed
[10] T.A. Hill, S.G. Stewart, S.P. Ackland, J. Gilbert, B. Sauer, J.A. Sakoff, A. McCluskey, Bioorg. Med. Chem. 15, 6126 (2007) http://dx.doi.org/10.1016/j.bmc.2007.06.03410.1016/j.bmc.2007.06.034Search in Google Scholar PubMed
[11] X. W. Liu, J. Li, H. Li, K.C. Zheng, H. Chao, L.N. Ji, J. Inorg. Biochem. 99, 2372 (2005) http://dx.doi.org/10.1016/j.jinorgbio.2005.09.00410.1016/j.jinorgbio.2005.09.004Search in Google Scholar
[12] S.G. Stewart, T.A. Hill, J. Gilbert, S.P. Ackland, J.A. Sakoff, A. McCluskey, Bioorg. Med. Chem. 15, 7301 (2007) http://dx.doi.org/10.1016/j.bmc.2007.08.02810.1016/j.bmc.2007.08.028Search in Google Scholar
[13] X.L. Zheng, H.X. Sun, X.L. Liu, Y.X. Chen, B.C. Qian, Acta Pharmacol. Sin. 25, 1090 (2004) Search in Google Scholar
[14] N. Niklas, O. Walter, R. Alsfasser, Eur. J. Inorg. Chem. 1723 (2000) 10.1002/1099-0682(200008)2000:8<1723::AID-EJIC1723>3.0.CO;2-NSearch in Google Scholar
[15] M. Bakir, O. Green, W.H. Mulder, J. Mol. Struct. 873, 17 (2008) http://dx.doi.org/10.1016/j.molstruc.2007.03.00110.1016/j.molstruc.2007.03.001Search in Google Scholar
[16] J.B. Chaires, N. Dattagupta, D.M. Crothers, Biochemistry 21, 3933 (1982) http://dx.doi.org/10.1021/bi00260a00510.1021/bi00260a005Search in Google Scholar
[17] A.K.D Mesmaeker, G. Orellana, J.K. Barton, N.J. Turro, Photochem. Photobiol. 52, 461 (1990) http://dx.doi.org/10.1111/j.1751-1097.1990.tb01787.x10.1111/j.1751-1097.1990.tb01787.xSearch in Google Scholar
[18] J.Z. Wu, L. Yuan, J.F. Wu, J. Inorg. Biochem. 99, 2211 (2005) http://dx.doi.org/10.1016/j.jinorgbio.2005.08.00210.1016/j.jinorgbio.2005.08.002Search in Google Scholar
[19] J.R. Lakowicz, G. Weber, Biochemistry 12, 4161 (1973) http://dx.doi.org/10.1021/bi00745a02010.1021/bi00745a020Search in Google Scholar
[20] B.C. Baguley, M.L. Bret, Biochemistry 23, 937 (1984) http://dx.doi.org/10.1021/bi00300a02210.1021/bi00300a022Search in Google Scholar
[21] S. Satyanarayana, J.C. Dabrowiak, J.B. Chaires, Biochemistry 32, 2573 (1993) http://dx.doi.org/10.1021/bi00061a01510.1021/bi00061a015Search in Google Scholar
[22] J.M. Kelly, A.B. Tossi, D.J. McConnell, C. ObUigin, Nucleic Acids Res. 13, 6017 (1985) http://dx.doi.org/10.1093/nar/13.17.601710.1093/nar/13.17.6017Search in Google Scholar PubMed PubMed Central
[23] M.A. Chowdhury, F. Huq, A. Abdullah, P. Beale, K. Fisher, J. Inorg. Biochem. 99, 1098 (2005) http://dx.doi.org/10.1016/j.jinorgbio.2005.02.00210.1016/j.jinorgbio.2005.02.002Search in Google Scholar PubMed
[24] Y. Baba, N. Hirukawa, N. Tanohira, M. Sodeoka, J. Am. Chem. Soc. 125, 9740 (2003) http://dx.doi.org/10.1021/ja034694y10.1021/ja034694ySearch in Google Scholar PubMed
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